A phase IB, open-label dose-escalating study of the oral angiogenesis inhibitor PTK787/ZK 222584 (PTK/ZK), in combination with FOLFOX4 chemotherapy in patients with advanced colorectal cancer

Annals of Oncology

Volumn 18, Issue 4, 2007, Pages 782-788

  Thomas, A L ^a,f   Trarbach, T ^b   Bartel, C ^c   Laurent, D ^d   Henry, A ^e   Poethig, M ^d   Wang, J ^e   Masson, E ^e   Steward, W ^a   Vanhoefer, U ^b   Wiedenmann, B ^c  

^a UNIVERSITY OF LEICESTER   (United Kingdom)

^b UNIVERSITY OF ESSEN MEDICAL SCHOOL   (Germany)

^c CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^d BAYER PHARMA AG   (Germany)

^e NOVARTIS PHARMA AG   (Switzerland)

^f LEICESTER ROYAL INFIRMARY   (United Kingdom)

Author keywords

Colorectal cancer; FOLFOX4 chemotherapy; Phase I; PTK ZK

Indexed keywords

FLUOROURACIL; FOLINIC ACID; OXALIPLATIN; VATALANIB;

ADULT; ADVANCED CANCER; AGED; ANEMIA; ANOREXIA; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTHRALGIA; ARTICLE; ATAXIA; CANCER COMBINATION CHEMOTHERAPY; CANCER SURVIVAL; CHEMOTHERAPY INDUCED EMESIS; CHILL; CLINICAL ARTICLE; CLINICAL PROTOCOL; CLINICAL TRIAL; COLORECTAL CANCER; CONSTIPATION; COORDINATION DISORDER; DEHYDRATION; DIARRHEA; DIZZINESS; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG ERUPTION; DRUG HALF LIFE; DRUG SAFETY; DRUG WITHDRAWAL; DYSPEPSIA; DYSPHASIA; FATIGUE; FEMALE; HUMAN; HYPERTENSION; LETHARGY; LUNG EMBOLISM; MALE; MAXIMUM PLASMA CONCENTRATION; MAXIMUM TOLERATED DOSE; MELENA; MULTICENTER STUDY; NAUSEA; NEUROPATHY; NEUTROPENIA; OPEN STUDY; PARESTHESIA; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; STOMATITIS; SYNCOPE; THROMBOCYTOPENIA; TREATMENT DURATION;

EID: 33947135447     PISSN: 09237534     EISSN: 15698041     Source Type: Journal    
DOI: 10.1093/annonc/mdl469     Document Type: Article

References (25)

1. Folkman J. Tumor angiogenesis: Therapeutic implications. N Engl J Med 1971; 285: 1182-1186.
2. Dvorak HF, Brown LF, Detmar M et al. Vascular permeability factor/ vascular endothelial growth factor, microvascular permeability, and angiogenesis. Am J Pathol 1995; 146: 1029-1039.
3. Shibuya M. Vascular endothelial growth factor receptor family genes: when did the three genes phylogenetically segregate? Biol Chem 2002; 383: 1573-1579.
4. Olszewski AJ, Grossbard ML, Kozuch PS. The horizon of antiangiogenic therapy for colorectal cancer. Oncology 2005; 19: 297-306.
5. Hurwitz HI, Fehrenbacher L, Hainsworth JD et al. Bevacizumab in combination with fluorouracil and leucovorin: An active regimen for first-line metastatic colorectal cancer. J Clin Oncol 2005; 23: 3502-3508.
6. Allen J, Bergsland EK. Angiogenesis in colorectal cancer: Therapeutic implications and future directions. Hematol Oncol Clin North Am 2004; 18: 1087-1119.
7. Scavelli C, Vacca A, Di Pietro G et al. Crosstalk between angiogenesis and lymphangiogenesis in tumor progression. Leukemia 2004; 18: 1054-1058.
8. Achen MG, Jeltsch M, Kukk E et al. Vascular endothelial growth factor D (VEGFD) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4). Proc Natl Acad Sci USA 1998; 95: 548-553.
9. He Y, Kozaki K, Karpanen T et al. Suppression of tumor lymphangiogenesis and lymph node metastases by blocking vascular endothelial growth factor receptor 3 signaling. J Natl Cancer Inst 2002; 94: 819-825.
10. Hess-Stump H, Haberey M, Thierauch KH. PTK787/ZK 222584, a tyrosine kinase inhibitor of all known VEGF receptors, represses tumor growth with high efficacy. Chembiochem 2005; 6: 550-557.
11. Wood JM, Bold G, Buchdunger E et al. PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth-factor induced responses and tumor growth after oral administration. Cancer Res 2000; 60: 2178-2189.
12. Drevs J, Muller-Driver R, Wittig C et al. PTK787/ZK 222584, a specific vascular endothelial growth factor-receptor tyrosine kinase inhibitor, affects the anatomy of the tumor vascular bed and the functional vascular properties as detected by dynamic-enhanced magnetic resonance imaging. Cancer Res 2002; 62: 4015-4022.
13. Morgan B, Thomas AL, Drevs J et al. Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmaceutical response of PTK787/ZK 222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases: Results from 2 phase 1 studies. J Clin Oncol 2003; 21: 3955-3964.
14. Thomas AL, Morgan B, Horsfield MA et al. Phase 1 study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of PTK787/ZK 222584 administered twice daily in patients with advanced cancer. J Clin Oncol 2005; 23: 4162-4171.
15. Brown LF, Berse B, Jackman BB et al. Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in adenocarcinomas of the gastrointestinal tract. Cancer Res 1993; 53: 4727-4735.
16. de Gramont A, Figer A, Seymour M et al. Leucovorin or fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 2000; 18: 2938-2947.
17. Grothey A. Clinical management of oxaliplatin-associated neurotoxicity. Clin Colorectal Cancer 2005; 5 (Suppl 1): S38-S46.
18. Green S, Weiss GR. Southwest Oncology Group standard response criteria, endpoint definitions and toxicity criteria. Invest New Drugs 1992; 10: 239-253.
19. Mross K, Drevs J, Müller M et al. Phase 1 clinical and pharmacokinetic study of PTK/ZK, a multiple VEGF receptor inhibitor, in patients with liver metastases from solid tumors. Eur J Cancer 2005; 41: 1291-1299.
20. Tournigand C, André T, Achille E et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: A randomized GERCOR study. J Clin Oncol 2004; 22: 229-237.
21. Zangari M, Anaissie E, Stopeck A et al. Phase II study of SU5416, a small molecule vascular endothelial growth factor tyrosine kinase receptor inhibitor, in patients with refractory multiple myeloma. Clin Cancer Res 2004; 10: 88-95.
22. Faivre S, Delbaldo C, Vera K et al. Safety, pharmacokinetic and antitumour activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. J Clin Oncol 2006; 24: 25-35.
23. Rugo HS, Herbst RS, Liu G et al. Phase I trial of the oral angiogenesis agent AG-013736 in patients with advanced solid tumors: Pharmacokinetic and clinical results. J Clin Oncol 2005; 23: 5474-5483.
24. Goldberg RM, Sargent DJ, Morton RF et al. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 2004; 22: 23-30.
25. Hecht JR, Trarbach T, Jaeger E et al. A randomized, double-blind, placebo-controlled, phase III study in patients (Pts) with metastatic adenocarcinoma of the colon or rectum receiving first-line chemotherapy with oxaliplatin/5-fluorouracil/leucovorin and PTK/787/ZK 222584 or placebo (CONFIRM-1). Proc Am Soc Clin Oncol 2005; 23: LBA3.